Gene-therapy results touted in 2 advanced-cancer cases

WASHINGTON — Researchers from the National Cancer Institute on Thursday reported they have successfully treated two patients with advanced cancer using gene therapy.

Two men, both with the rapidly growing skin cancer melanoma, were given immune-system cells taken from their own blood and engineered to attack their tumors. They are alive, with no evidence of cancer, 18 months later. Fifteen other patients who got the same treatment died.

The senior author of the study and others cautioned it would take several years to translate the treatment into a practical therapy.

The report, published online by the journal Science, is the latest result of a 30-year effort by Dr. Steven Rosenberg to find ways to manipulate the human immune system to fight cancer.

Four years ago, Rosenberg, a surgeon, and his colleagues treated a group of melanoma patients with naturally occurring anti-cancer cells extracted from their tumors, and some of those patients also have had long-term disappearance of their cancers.

The new study, however, is believed to be the first time genetically engineered immune-system cells — specifically, T lymphocytes — produced the same effect.

Neither Rosenberg nor others would describe the two patients as "cured." At least five years would need to pass before such a declaration would be considered. And cancer sometimes returns even after much more time has passed.

Melanoma accounts for only 4 percent of skin cancer but it is the most lethal type. More than 62,000 patients will be diagnosed with melanoma this year, and 7,910 people will die, according to the American Cancer Society.

Gene therapy was once viewed as the great hope for treating, or even curing, a long list of diseases. But tests of the concept since the late 1980s have been overwhelmingly disappointing.

"I do consider this a proof of the principle that it can work," Rosenberg said Thursday. "I have every expectation that we can get it to work better."

Response by others in the field was positive but not effusive.

"I think it is an important landmark to see some cancer patients respond to a gene therapy — finally," said Patrick Hwu, a physician and gene-therapy researcher at University of Texas M.D. Anderson Cancer Center in Houston, who was not involved in the new study. "I think that clearly all of us want to do better than two out of 17."

Michael Lotze, professor of surgery and bioengineering at the University of Pittsburgh, said "the work is heroic. The question is, does it advance the field in a major way?"

While the good response in two patients is encouraging, "in terms of response rates, the overwhelming data is that T cells, even in high numbers, are inadequate to mediate sufficient anti-tumor effects," Lotze said.

In the study, Rosenberg and his colleagues took lymphocytes from the blood and inserted into them genes for a receptor capable of "recognizing" a protein on melanoma cells called MART-1. This would allow the lymphocyte to attach to a tumor cell and kill it.

The patients, all of whom had previously undergone surgery and immune-based treatments, got chemotherapy to temporarily wipe out their immune systems.

The engineered cells were then reinjected, with the hope they would proliferate as the immune system recovered. The patients also received Interleukin-2, which is a cytokine, or immune-system hormone.

One of the patients, a 52-year-old man, had melanoma in his neck, liver and armpit. It disappeared everyplace but one spot in the liver; surgeons removed that area. The other man, age 30, had tumor in his lungs and just outside them in the middle of the chest. His cancer disappeared also.

The paper published Thursday provided few details of previous treatment the men had received. Rosenberg also did not analyze any of the reintroduced lymphocytes to see if, in fact, they had the ability to kill cancer cells.

Because of that, it is difficult to say with certainty that the engineered cells were responsible for the tumors' disappearance. However, Lotze, the Pittsburgh expert, said "it is unlikely" it was due to other treatments.

Rosenberg said he and his colleagues have engineered lymphocytes to recognize tumor markers, or antigens, found in about half of all cancers, including breast, colon and lung cancer.

He said many of the modified cells have a much better ability to bind to tumor cells than the anti-melanoma cells he used in the study reported Thursday, which was conducted two years ago.

The research team recently applied to the Food and Drug Administration (FDA) to try the new cells in about 100 patients. The FDA is expected to respond to the request by mid-September.

Material from The Associated Press and Los Angeles Times is included in this report.